PUR2_DROPS
ID PUR2_DROPS Reviewed; 1364 AA.
AC P16340; Q29P31; Q56RW7;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 27-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Trifunctional purine biosynthetic protein adenosine-3;
DE Includes:
DE RecName: Full=Phosphoribosylamine--glycine ligase;
DE EC=6.3.4.13 {ECO:0000250|UniProtKB:P00967};
DE AltName: Full=Glycinamide ribonucleotide synthetase;
DE Short=GARS;
DE AltName: Full=Phosphoribosylglycinamide synthetase;
DE Includes:
DE RecName: Full=Phosphoribosylformylglycinamidine cyclo-ligase;
DE EC=6.3.3.1 {ECO:0000250|UniProtKB:P00967};
DE AltName: Full=AIR synthase;
DE Short=AIRS;
DE AltName: Full=Phosphoribosyl-aminoimidazole synthetase;
DE Includes:
DE RecName: Full=Phosphoribosylglycinamide formyltransferase;
DE EC=2.1.2.2 {ECO:0000250|UniProtKB:P00967};
DE AltName: Full=5'-phosphoribosylglycinamide transformylase;
DE AltName: Full=GAR transformylase;
DE Short=GART;
GN Name=ade3; Synonyms=gart; ORFNames=GA16345;
OS Drosophila pseudoobscura pseudoobscura (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=46245;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=EST10;
RX PubMed=3123310; DOI=10.1093/genetics/117.4.711;
RA Henikoff S., Eghtedarzadeh M.K.;
RT "Conserved arrangement of nested genes at the Drosophila Gart locus.";
RL Genetics 117:711-725(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MV2-25 / Tucson 14011-0121.94;
RX PubMed=15632085; DOI=10.1101/gr.3059305;
RA Richards S., Liu Y., Bettencourt B.R., Hradecky P., Letovsky S.,
RA Nielsen R., Thornton K., Hubisz M.J., Chen R., Meisel R.P., Couronne O.,
RA Hua S., Smith M.A., Zhang P., Liu J., Bussemaker H.J., van Batenburg M.F.,
RA Howells S.L., Scherer S.E., Sodergren E., Matthews B.B., Crosby M.A.,
RA Schroeder A.J., Ortiz-Barrientos D., Rives C.M., Metzker M.L., Muzny D.M.,
RA Scott G., Steffen D., Wheeler D.A., Worley K.C., Havlak P., Durbin K.J.,
RA Egan A., Gill R., Hume J., Morgan M.B., Miner G., Hamilton C., Huang Y.,
RA Waldron L., Verduzco D., Clerc-Blankenburg K.P., Dubchak I., Noor M.A.F.,
RA Anderson W., White K.P., Clark A.G., Schaeffer S.W., Gelbart W.M.,
RA Weinstock G.M., Gibbs R.A.;
RT "Comparative genome sequencing of Drosophila pseudoobscura: chromosomal,
RT gene, and cis-element evolution.";
RL Genome Res. 15:1-18(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 107-565.
RX PubMed=15545653; DOI=10.1534/genetics.104.033068;
RA Bartolome C., Maside X., Yi S., Grant A.L., Charlesworth B.;
RT "Patterns of selection on synonymous and nonsynonymous variants in
RT Drosophila miranda.";
RL Genetics 169:1495-1507(2005).
CC -!- FUNCTION: Trifunctional enzyme required for de novo purine
CC biosynthesis. {ECO:0000250|UniProtKB:P00967}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-phospho-beta-D-ribosylamine + ATP + glycine = ADP + H(+) +
CC N(1)-(5-phospho-beta-D-ribosyl)glycinamide + phosphate;
CC Xref=Rhea:RHEA:17453, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57305, ChEBI:CHEBI:58681,
CC ChEBI:CHEBI:143788, ChEBI:CHEBI:456216; EC=6.3.4.13;
CC Evidence={ECO:0000250|UniProtKB:P00967};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-formamido-N(1)-(5-O-phospho-beta-D-ribosyl)acetamidine + ATP
CC = 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:23032, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:137981,
CC ChEBI:CHEBI:147287, ChEBI:CHEBI:456216; EC=6.3.3.1;
CC Evidence={ECO:0000250|UniProtKB:P00967};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-10-formyltetrahydrofolate + N(1)-(5-phospho-beta-D-
CC ribosyl)glycinamide = (6S)-5,6,7,8-tetrahydrofolate + H(+) + N(2)-
CC formyl-N(1)-(5-phospho-beta-D-ribosyl)glycinamide;
CC Xref=Rhea:RHEA:15053, ChEBI:CHEBI:15378, ChEBI:CHEBI:57453,
CC ChEBI:CHEBI:57454, ChEBI:CHEBI:143788, ChEBI:CHEBI:147286;
CC EC=2.1.2.2; Evidence={ECO:0000250|UniProtKB:P00967};
CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; 5-
CC amino-1-(5-phospho-D-ribosyl)imidazole from N(2)-formyl-N(1)-(5-
CC phospho-D-ribosyl)glycinamide: step 2/2.
CC {ECO:0000250|UniProtKB:P00967}.
CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; N(1)-
CC (5-phospho-D-ribosyl)glycinamide from 5-phospho-alpha-D-ribose 1-
CC diphosphate: step 2/2. {ECO:0000250|UniProtKB:P00967}.
CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; N(2)-
CC formyl-N(1)-(5-phospho-D-ribosyl)glycinamide from N(1)-(5-phospho-D-
CC ribosyl)glycinamide (10-formyl THF route): step 1/1.
CC {ECO:0000250|UniProtKB:P00967}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P16340-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P16340-2; Sequence=VSP_005514, VSP_005515;
CC -!- SIMILARITY: In the N-terminal section; belongs to the GARS family.
CC {ECO:0000305}.
CC -!- SIMILARITY: In the central section; belongs to the AIR synthase family.
CC {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the GART family.
CC {ECO:0000305}.
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DR EMBL; X06285; CAA29611.1; -; Genomic_DNA.
DR EMBL; CH379058; EAL34461.2; -; Genomic_DNA.
DR EMBL; AY754390; AAX12966.1; -; Genomic_DNA.
DR PIR; S01204; AJFFPP.
DR RefSeq; XP_001357392.2; XM_001357356.3.
DR AlphaFoldDB; P16340; -.
DR SMR; P16340; -.
DR STRING; 7237.FBpp0279413; -.
DR EnsemblMetazoa; FBtr0280975; FBpp0279413; FBgn0012717. [P16340-1]
DR GeneID; 4817813; -.
DR KEGG; dpo:Dpse_GA25439; -.
DR eggNOG; KOG0237; Eukaryota.
DR eggNOG; KOG3076; Eukaryota.
DR HOGENOM; CLU_005361_0_1_1; -.
DR InParanoid; P16340; -.
DR OMA; EVMQACC; -.
DR UniPathway; UPA00074; UER00125.
DR UniPathway; UPA00074; UER00126.
DR UniPathway; UPA00074; UER00129.
DR Proteomes; UP000001819; Chromosome 4.
DR Bgee; FBgn0012717; Expressed in female reproductive system and 2 other tissues.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004637; F:phosphoribosylamine-glycine ligase activity; IEA:UniProtKB-EC.
DR GO; GO:0004641; F:phosphoribosylformylglycinamidine cyclo-ligase activity; IEA:UniProtKB-EC.
DR GO; GO:0004644; F:phosphoribosylglycinamide formyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006189; P:'de novo' IMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009113; P:purine nucleobase biosynthetic process; IEA:InterPro.
DR CDD; cd08645; FMT_core_GART; 1.
DR CDD; cd02196; PurM; 2.
DR Gene3D; 3.30.1330.10; -; 2.
DR Gene3D; 3.30.1490.20; -; 1.
DR Gene3D; 3.90.600.10; -; 1.
DR Gene3D; 3.90.650.10; -; 2.
DR HAMAP; MF_00741; AIRS; 1.
DR HAMAP; MF_00138; GARS; 1.
DR HAMAP; MF_01930; PurN; 1.
DR InterPro; IPR011761; ATP-grasp.
DR InterPro; IPR013815; ATP_grasp_subdomain_1.
DR InterPro; IPR002376; Formyl_transf_N.
DR InterPro; IPR036477; Formyl_transf_N_sf.
DR InterPro; IPR004607; GART.
DR InterPro; IPR001555; GART_AS.
DR InterPro; IPR016185; PreATP-grasp_dom_sf.
DR InterPro; IPR020561; PRibGlycinamid_synth_ATP-grasp.
DR InterPro; IPR000115; PRibGlycinamide_synth.
DR InterPro; IPR020560; PRibGlycinamide_synth_C-dom.
DR InterPro; IPR037123; PRibGlycinamide_synth_C_sf.
DR InterPro; IPR020559; PRibGlycinamide_synth_CS.
DR InterPro; IPR020562; PRibGlycinamide_synth_N.
DR InterPro; IPR010918; PurM-like_C_dom.
DR InterPro; IPR036676; PurM-like_C_sf.
DR InterPro; IPR016188; PurM-like_N.
DR InterPro; IPR036921; PurM-like_N_sf.
DR InterPro; IPR004733; PurM_cligase.
DR InterPro; IPR011054; Rudment_hybrid_motif.
DR PANTHER; PTHR10520; PTHR10520; 2.
DR Pfam; PF00586; AIRS; 2.
DR Pfam; PF02769; AIRS_C; 2.
DR Pfam; PF00551; Formyl_trans_N; 1.
DR Pfam; PF01071; GARS_A; 1.
DR Pfam; PF02843; GARS_C; 1.
DR Pfam; PF02844; GARS_N; 1.
DR SMART; SM01210; GARS_C; 1.
DR SUPFAM; SSF51246; SSF51246; 1.
DR SUPFAM; SSF52440; SSF52440; 1.
DR SUPFAM; SSF53328; SSF53328; 1.
DR SUPFAM; SSF55326; SSF55326; 2.
DR SUPFAM; SSF56042; SSF56042; 2.
DR TIGRFAMs; TIGR00877; purD; 1.
DR TIGRFAMs; TIGR00878; purM; 2.
DR TIGRFAMs; TIGR00639; PurN; 1.
DR PROSITE; PS50975; ATP_GRASP; 1.
DR PROSITE; PS00184; GARS; 1.
DR PROSITE; PS00373; GART; 1.
PE 3: Inferred from homology;
KW Alternative splicing; ATP-binding; Ligase; Manganese; Metal-binding;
KW Multifunctional enzyme; Nucleotide-binding; Purine biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1..1364
FT /note="Trifunctional purine biosynthetic protein adenosine-
FT 3"
FT /id="PRO_0000074935"
FT DOMAIN 114..321
FT /note="ATP-grasp"
FT REGION 435..1154
FT /note="AIRS"
FT REGION 1155..1364
FT /note="GART"
FT ACT_SITE 1265
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 140..202
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 291
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT BINDING 293
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT BINDING 1166..1168
FT /ligand="N(1)-(5-phospho-beta-D-ribosyl)glycinamide"
FT /ligand_id="ChEBI:CHEBI:143788"
FT /evidence="ECO:0000250"
FT BINDING 1221
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250"
FT BINDING 1246..1249
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250"
FT BINDING 1263
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250"
FT BINDING 1297..1301
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250"
FT BINDING 1327..1330
FT /ligand="N(1)-(5-phospho-beta-D-ribosyl)glycinamide"
FT /ligand_id="ChEBI:CHEBI:143788"
FT /evidence="ECO:0000250"
FT SITE 1301
FT /note="Raises pKa of active site His"
FT /evidence="ECO:0000250"
FT VAR_SEQ 434
FT /note="I -> M (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_005514"
FT VAR_SEQ 435..1364
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_005515"
FT CONFLICT 327
FT /note="L -> M (in Ref. 3; AAX12966)"
FT /evidence="ECO:0000305"
FT CONFLICT 425
FT /note="T -> M (in Ref. 3; AAX12966)"
FT /evidence="ECO:0000305"
FT CONFLICT 805
FT /note="T -> S (in Ref. 1; CAA29611)"
FT /evidence="ECO:0000305"
FT CONFLICT 956
FT /note="G -> A (in Ref. 1; CAA29611)"
FT /evidence="ECO:0000305"
FT CONFLICT 1145
FT /note="A -> T (in Ref. 1; CAA29611)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1364 AA; 145663 MW; 4BDF1C7BD435E642 CRC64;
MSHSVLVIGS GGREHAICWK LSQSTLVKQI YALPGSFGIQ QVEKCRNLDA KVLDPKDFEA
IAKWSKKNEI SLVVVGPEDP LALGLGDVLQ KEGIPCFGPG KQGAQIEADK KWAKDFMLRH
GIPTARYESF TDTNKAKAFI RSAPYQALVV KAAGLAAGKG VVVAANVDEA CQAVDEILGD
LKYGQAGATL VVEELLEGEE ISVLAFTDGK SVRAMLPAQD HKRLGNGDTG PNTGGMGAYC
PCPLISQPAL ELVQRAVLER AVQGLIKERI TYQGVLYAGL MLTRDGPRVL EFNCRFGDPE
TQVILPLLET DLFEVMQACC SGQLDRLPLQ WRSGVSAVGV VLASAGYPET STKGCLITGL
PDVNSPTQLI FHSGLSVNKQ KEALTNGGRV LIAIALDASL KEAAAKATKL AGTITFAGTG
AQYRTDIAQK AFKIAIATAP GLSYKDSGVD IDAGDALVQR IKPLSRGTQR PGVLGGLGGF
GGLFRLKDLS YKEPVIAEAT QGVGAKIQLA LQNELYENIG YDLFAMSAND LLELGAEPVA
FLDYIACGKL HVPLAAQLVK GMADGCRDAK CALVGGETAE MPSLYAPGQH DMAGYCVGIV
EQARVLPRFD LYEPEDLLVG LPSSGLHCAG FNEILTQLAA SKVNLKECSP VGGGKHGLSL
AQVLGTPTRL YVQQLLPHLQ AGNQIKAVAH VTHGLLHDVQ RLLPEGFEVT LDFGAVPVPD
VFGWLAGQLQ LSAQTLLERH NCGIGMVLVL PQSSLLWRTA LPGAKVLGVL NRQAKASGGA
PRVKVRNFVE QLQKLAAPFG GLGETQLPEE VKDVPSSGVK ATTREECFEN AVGRRLTRVP
NHYVDPILIL GTDGVGTKLK IAQQTHRNAS VGIDLVAMCV NDILCNGAEP FSFSSYYACG
KWQAALAAEV NAGVQEGASQ ANSSFVASHS AALPLLYEPQ VYDLAGFALG IAERSGILPR
LDEIQPGDVL IGLPSSGVHS NGFSLVHAVL KRAGLGLNDR APFSEKTLGE ELLVPTKIYV
KALSALLSRP NHGIKALAHI TGGGLSENIP RVLRKELAVR LDANKYPLPP VFAWLAAAGN
ISSTELQRTY NCGLGLVLVV GATEVDGVLR ELRYPQRASV VGEVVARKDP KKPQVVVQNF
EASLARTQRM LSQPRKRVAV LISGKGSNLQ ALIDAIRDSA QGVYAEIVLV ISNKAGVLGL
ERAAKAGIPS MVISHKDFPS REVYDVELTR HLKTARVEFI CLAGFMRILS VPFVREWRGR
LINIHPSLLP KFPGLHVQKQ ALEAGETESG CTVHYVDEGV DTGAIIVQAA VPILPGDDEE
TLTQRIHYAE HWAFPRALAL LASGALRRVS EVKKEAPKDI KDSQ
